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Decoding Plasma Cell Maturation Dynamics with BCMA

ABSTRACT: Decoding Plasma Cell Maturation Dynamics with BCMA

PROVIDER: PRJNA1159213 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30621245_1.fastq.gz	Fastqsanger.gz
	SRR30621245_2.fastq.gz	Fastqsanger.gz
	SRR30621246_1.fastq.gz	Fastqsanger.gz
	SRR30621246_2.fastq.gz	Fastqsanger.gz
	SRR30621247_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

Decoding Plasma Cell Maturation Dynamics with BCMA

Project description:Plasma cells provide protective antibodies following an infection or vaccination. A network of intrinsic and extrinsic factors fine-tunes the generation of a heterogenous plasma cell pool with varying metabolic requirements, transcriptional profiles and lifespans. Among these intrinsic factors, the B cell maturation antigen (BCMA) has been implicated in APRIL-mediated survival of long-lived plasma cells. Therefore, we introduced a tdTomato reporter into the Tnfrsf17 (BCMA) locus, to decode the developmental steps behind the generation of mature plasma cell subsets. We demonstrate that the BCMA:Tom reporter is exclusively detected in plasma cells, with its expression differing between IgH isotypes and increasing with plasma cell maturity. Combined with a Blimp1-GFP reporter, the BCMA:Tom reporter allowed us to track the step-wise maturation from newly formed to late plasma cells in various plasma cell subpopulations. Notably, in vitro-stimulated B cells induce BCMA only after adoptive transfer into recipient mice, emphasizing the impact of the in vivo microenvironment in establishing a mature plasma cell compartment. The BCMA:Tom reporter mouse provides a robust tool for tracking plasma cell development and maturation with flow cytometry or advanced imaging techniques, enabling a deeper understanding of the mechanisms regulating plasma cell heterogeneity and longevity.

2025-04-02 | GSE276846 | GEO

The B cell maturation antigen (BCMA) is dispensable for long-lived plasma cell survival

Project description:Survival of antibody-secreting plasma cells is a prerequisite to establish long-lasting humoral immune protection. The B cell maturation antigen (BCMA) has been proposed to promote APRIL-mediated survival signals in plasma cells. However, the extensive shedding of murine BCMA from the plasma cell surface raises doubts about its ability to function as a signaling receptor. To unequivocally establish whether BCMA is required for long-lived plasma cell survival, we established two independent BCMA-deficient mouse lines and analyzed the survival of antigen-specific plasma cells after immunization. In contrast to published data, we found comparable numbers of long-lived antigen-specific plasma cells after primary and secondary protein and mRNA immunizations in BCMA-deficient mice. In addition, wildtype and BCMA-deficient plasma cells showed comparable transcriptome profiles with no indication for reduced survival signaling. Interestingly, total plasma cell numbers were increased after boost immunization in bone marrow and mesenteric lymph nodes of BCMA-deficient mice. Therefore, BCMA has no intrinsic role in maintaining long-lived plasma cells. We propose a function of BCMA limited to acting as a soluble decoy receptor for APRIL and fine-tuneing the size of the plasma cell population by limiting the availability of survival factors. This finding removes a piece of the puzzle of the mechanisms that contribute to long-lived plasma cell survival.

2025-06-30 | GSE277098 | GEO

The B cell maturation antigen (BCMA) is dispensable for long-lived plasma cell survival

Project description:The B cell maturation antigen (BCMA) is dispensable for long-lived plasma cell survival

| PRJNA1160792 | ENA

BCMA ubiquitylation in multiple myeloma

Project description:Mass spectrometric analysis of MM cell-purified B-cell maturation antigen (BCMA) protein to identify ubiquitylation sites.

2025-07-29 | PXD056372 | Pride

Maturation of Long Lived Plasma cells

Project description:Maturation of Long Lived Plasma cells

| PRJNA913594 | ENA

Translational dynamics during seed maturation

Project description:Translational dynamics during seed maturation

| PRJNA524885 | ENA

Single-cell transcriptomic sequencing of BCMA CAR-T cells during CAR-T therapy in refractory primary plasma cell leukemia

Project description:Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the clinical treatment of hematological malignancies due to the prominent anti-tumor effects. B-cell maturation antigen (BCMA) CAR-T cells have demonstrated promising effects in patients with relapsed/refractory multiple myeloma. However, the dynamics of CAR-T cell proliferation and cytotoxicity in a patient remains largely unexplored. Single-cell RNA sequencing samples were collected at three phases: CAR-T products before infusion, CAR-T on day 8 after infusion, and CAR-T on day 15 after infusion. After obtaining the PBMCs for each phase, CAR-T and endogenous T cells were collected by fluorescence-activated cell sorting with anti-Mouse IgG Biotin, FITC Streptavidin, and anti-human CD3 APC.

2020-10-01 | GSE151310 | GEO

Translational dynamics during seed maturation

Project description:We analysed the polysomal mRNA and total mRNA during Col-0 seed maturation The aim was to investigate the translational dynamics during seed maturation.

2019-09-28 | GSE127509 | GEO

Neurocognitive and hypokinetic movement disorder with features of parkinsonism following BCMA-targeting CAR-T cell therapy

Project description:B-cell maturation antigen (BCMA) is a prominent tumor-associated target for chimeric antigen receptor (CAR)-T cell therapy in multiple myeloma (MM). We describe the case of a MM patient, enrolled in the CARTITUDE-1 trial (NCT03548207), who developed a progressive movement disorder with features of parkinsonism approximately three months after BCMA-targeted ciltacabtagene autoleucel CAR-T cell infusion, associated with CAR-T cell persistence in the blood and cerebrospinal fluid, and basal ganglia lymphocytic infiltration. We demonstrate BCMA expression on neurons and astrocytes in the basal ganglia of the patient. Public transcriptomic datasets further confirm BCMA RNA expression in the caudate of normal human brains, suggesting this may be an on-target effect of anti-BCMA therapy. Given reports of three patients with grade ≥3 parkinsonism on the phase 2 cilta-cel trial and of grade 3 parkinsonism in the idecabtagene vicleucel (ide-cel) package insert, our findings support close neurological monitoring of patients on BCMA-targeted T cell therapies.

2021-08-27 | GSE182527 | GEO

Homozygous BCMA gene deletion in response to anti-BCMA CAR T cells in a patient with Multiple Myeloma

Project description:Chimeric antigen receptor T-cells (CAR-T) targeting B-cell-maturating-antigen (TNRFSF17, BCMA) show unprecedented overall response rates of up to 100% in heavily pretreated relapsed-refractory Multiple Myeloma (RRMM). However, the efficiency of the treatment is hindered by the rapid emergence of tumor-intrinsic mechanisms of resistance. We herein describe a patient with RRMM and extramedullary disease (EMD) who underwent Idecabtagene vicleucel BCMA CAR-T therapy. The patient rapidly achieved very good partial response including full resolution of EMD, but aggressively relapsed 5 months after CAR T cell infusion. Single cell RNA sequencing and immunohistochemistry on the re-emerging tumor cells demonstrated loss of target expression on mRNA and protein levels, and whole genome sequencing revealed the homozygous deletion of Chr 16p1313, including the BCMA locus. Clonal heterogeneity of BCMA could be observed in 32 RRMM patients from our institution. In three of them heterozygous deletion of BCMA could be confirmed, with none of them having underwent prior anti-BCMA therapy. Thus, our report not only provides first evidence of BCMA loss as the underlying mechanism of disease relapse following BCMA targeted immunotherapy in MM. It furthermore identifies a subset of patients at risk to develop biallelic BCMA inactivation thus linking genomic instability in MM to relapse from targeted immunotherapies.

2020-12-30 | GSE143317 | GEO

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